Electrophysiological and biochemical methods will be employed to investigate the association between acetylcholine (ACh) secretion and the release of adenosine triphosphate (ATP) and derivatives from motor nerve endings in rat and mouse skeletal muscle. Alterations in spontaneous and neurally evoked ACh output will be produced by changing the ionic composition of the bathing medium (e.g., adding La III, altering the concentration of Ca II, substituting Ba II for Ca II) and the release of ATP and derivatives will be assayed by firefly luciferase and paper chromatographic methods. The effects of procedures frequently used to study the 'trophic' influences of nerve on muscle (e.g., denervation and treatment with botulinum toxin or colchicine) will be studied with the hope of elucidating whether or not ATP release is associated with the trophic process. BIBLIOGRAPHIC REFERENCE: Silinsky, E. M. (1977) Can barium support the release of acetylcholine by nerve impulses? Brit J. Pharmacol 59:215-217.